Novel cancer gene discovery using a forward genetic screen in RCAS-PDGFB-driven gliomas.
Neuro Oncol
; 25(1): 97-107, 2023 01 05.
Article
de En
| MEDLINE
| ID: mdl-35738865
ABSTRACT
BACKGROUND:
Malignant gliomas, the most common malignant brain tumors in adults, represent a heterogeneous group of diseases with poor prognosis. Retroviruses can cause permanent genetic alterations that modify genes close to the viral integration site.METHODS:
Here we describe the use of a high-throughput pipeline coupled to the commonly used tissue-specific retroviral RCAS-TVA mouse tumor model system. Utilizing next-generation sequencing, we show that retroviral integration sites can be reproducibly detected in malignant stem cell lines generated from RCAS-PDGFB-driven glioma biopsies.RESULTS:
A large fraction of common integration sites contained genes that have been dysregulated or misexpressed in glioma. Others overlapped with loci identified in previous glioma-related forward genetic screens, but several novel putative cancer-causing genes were also found. Integrating retroviral tagging and clinical data, Ppfibp1 was highlighted as a frequently tagged novel glioma-causing gene. Retroviral integrations into the locus resulted in Ppfibp1 upregulation, and Ppfibp1-tagged cells generated tumors with shorter latency on orthotopic transplantation. In human gliomas, increased PPFIBP1 expression was significantly linked to poor prognosis and PDGF treatment resistance.CONCLUSIONS:
Altogether, the current study has demonstrated a novel approach to tagging glioma genes via forward genetics, validating previous results, and identifying PPFIBP1 as a putative oncogene in gliomagenesis.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs du cerveau
/
Gliome
Limites:
Animals
/
Humans
Langue:
En
Journal:
Neuro Oncol
Sujet du journal:
NEOPLASIAS
/
NEUROLOGIA
Année:
2023
Type de document:
Article
Pays d'affiliation:
Suède